Development Of Axially Chiral Cyclo-Biphenyldiol Ligands With Adjustable Dihedral Angles

Asymmetric synthesis is an important field in organic chemistry.In the previous asymmetric organic synthesis,transition metal-catalyzed asymmetric reactions are most often used.Therefore,development of chiral ligands has been a key issue for obtaining high reactivity and enantioselectivity.It is well known that the axially chiral biaryldiols are a kind of key cores and their modification has provided diverse excellent supporting ligands.The most prominent axially chiral ligand cores should be[1,1'-naphenyl]-2,2'-diol(BINOL)and 1,1'-spirobiindane-7,7'-diol(SPINOL),and their derivatives have been extensively evaluated as the versatile chiral ligands in asymmetric transformations.However,the catalytic reactivity and enantioselectivity are generally substrate-dependent,and there still is not an omnipotent ligand in dealing with the many challenging transition metal-catalyzed asymmetric transformations thus far because subtle variations in geometric,steric,and/or electronic properties of chiral ligands can cause dramatic changes of reactivity and enantioselectivity.In this dissertation,we investigated a kind of novel axially chiral cyclo-[1,1'-biphenyl]-2,2'-diol ligands with adjustable dihedral angles by varying the chain length of the full-carbon 6,6'-tether,and eight,nine,and ten-membered cyclo-ligands were prepared and evaluated in the asymmetric transformations.Some results were obtained as follows:A kind of novel axially chiral cyclo-[1,1'-biphenyl]-2,2'-diol ligands with adjustable dihedral angles have been developed by varying the 6,6'-bridge chain length.Eight,nine and ten-membered cyclo-ligands were designed and prepared,their structures and absolute configurations were identified by nuclear magnetic resonance,mass spectrometry,X-ray diffraction,polarimeter and circular dichroism analysis,and their enantiomeric purity was determined by chiral HPLC.A highly enantioselective addition of diethylzinc to aldehydes has been developed in the presence of axially chiral cyclo-[1,1'-biphenyl]-2,2'-diol ligands.The protocol used titanium tetraisopropoxide as the Lewis acid,our newly developed chiral cyclo-[1,1'-biphenyl]-2,2'-diols as the ligands,and the reaction was performed well in anhydrous dichloromethane at-20 ~oC.All ligands exhibited high reactivity,but the enantioselectivity showed remarkable difference.The results indicated that the fine regulation of dihedral angles by varying bridge chain length was effective in asymmetric synthesis.The reaction can tolerate various functional groups including ether,C-F bond,C-Cl bond,C-Br bond and S-heterocycle.A highly enantioselective copper-catalyzed addition of organometallic reagents to enones has been developed in the presence of axially chiral cyclic phosphoramidite ligands.Twelve axially chiral cyclic phosphoramidite ligands were prepared,and they were used in copper-catalyzed enantioselective addition of organometallic reagents to enones.The results showed that the fine regulation of dihedral angles by varying the bridge chain length could change enantioselective level,and two chiral cyclic phosphoramidites with nine-membered ring were optimal ligands.The method exhibits some advantages including using readily available alkenes and enones as the starting materials,application of alkylmetal agents generated in situ from alkenes,room temperature condition,and high levels of enantioselectivity.All the results show that our newly developed axially chiral cyclo-biphenyldiols will be of great application potential in asymmetric synthesis.